Due to heterogeneous multifocal nature of prostate cancer (PCa), there is currently a lack of biomarkers that stably distinguish it from benign prostatic hyperplasia (BPH), predict clinical outcome and guide the choice of optimal treatment. In this study RNA-seq analysis was applied to formalin-fixed paraffin-embedded (FFPE) tumor and matched normal tissue samples collected from Russian patients with PCa and BPH. We identified 3384 genes differentially expressed (DE) (FDR < 0.05) between tumor tissue of PCa patients and adjacent normal tissue as well as both tissue types from BPH patients. Overexpression of four of the discovered genes (ANKRD34B, NEK5, KCNG3, and PTPRT) was validated by RT-qPCR. Furthermore, the enrichment analysis of overrepresented microRNA and transcription factor (TF) recognition sites within DE genes revealed common regulatory elements of which 13 microRNAs and 53 TFs were thus linked to PCa for the first time. Moreover, 8 of these TFs (FOXJ2, GATA6, NFE2L1, NFIL3, PRRX2, TEF, EBF2 and ZBTB18) were found to be differentially expressed in this study making them not only candidate biomarkers of prostate cancer but also potential therapeutic targets.
Current prostate cancer (PCa) diagnostic tests suffer from insufficient sensitivity and specificity. Novel biomarkers that can be detected by minimally invasive methods are of a particular value. Here we provide two datasets. The first one is on the whole transcriptome profiling by RNA-seq of urine and plasma obtained from patients with PCa and benign prostatic hyperplasia (BPH). The second one represents targeted sequencing of DNA from urine and plasma of patients with PCa and BPH. Both datasets are available at NCBI Sequence Read Archive under Accession No. SRP093707 and No. SRP093842 respectively.
The marine bivalves, mussels Crenomytilus grayanus (Dunker, 1853) and scallops Swiftopecten swifti (Bernardi, 1858), were in vivo exposed to 12-14 nm multi-walled carbon nanotubes (MWNTs) for up to 48 h. Microscopic analysis in combination with the RAMAN spectrophotometry revealed the MWNT aggregates on the gills surface and inside the gut of all exposed individuals. After 48 h exposure, there were no changes in the total cell count, the average cell size and granularity in the hemolymph of mussels, while in the scallops the total hemocyte count was significantly reduced, and the average hemocyte granularity increased. Biochemical markers of oxidative stress (activity of glutathione-S-transferase and catalase, concentration of reduced glutathione, and the degree of lipid peroxidation) did not change significantly in the digestive gland of both mussels and scallops. In hemolymph, catalase activity increased as compared to control in both mussels and scallops. Moreover, concentration of reduced glutathione increased in hemolymph of scallops on the second day of exposure to MWNTs. The data obtained indicate that MWNTs may affect different bivalve mollusks more or less strongly under the same exposure conditions.
The RNA-seq approach for prostate cancer candidate RNA biomarkers screening in plasma and urine obtained by minimally invasive or noninvasive methods is proved to be feasible. Significant amount of RNA biomarkers associated with prostate cancer according to the literature were found in plasma and urine samples obtained from patients with benign prostatic hyperplasia (BPH). The number of detected markers was shown to vary in accordance with method of library preparation used for transcriptome profiling. The detection of known RNA biomarkers for prostate cancer in urine and plasma samples shows the feasibility of such method for minimally invasive diagnostics. The fact of presence of the same RNA biomarkers in samples from patients with BPH suggests their possible lack of specificity and confirms the need for further research in this area.
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